Abstract 2197: Comparative genomic profiling and disease monitoring in unresectable gastric and colon cancer
Authors: Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia
Journal: Cancer Research (2023)

Abstract Introduction: Molecular characteristics have significant clinical values in cancer distinguishing, treatment selection, and disease monitoring across large numbers of tumors. Previous studies have revealed the molecular classification of GI tract tumors through biomarkers such as gene alternations, MSI, EBV, and chromosomal instability (CIN). However, the clinical utility of these biomarkers remained limited. Here we reported a comprehensive genomic profiling study, comparing molecular characteristics between unresectable gastric and colon cancer patients. The study also investigated the potential use of molecular biomarkers for longitudinal disease monitoring. Methods: The prospective study planned to collect tissue and plasma samples from 200 unresectable GI tract cancer patients. Currently, 17 gastric cancer patients and 11 colon cancer patients were enrolled. Baseline tumor tissue samples were collected from 19 patients and baseline plasma samples were collected from 9 patients whose tissue biopsies were unavailable. Patients were then treated with targeted and chemo- therapies. Among the patients whose baseline plasma samples were collected, longitudinal plasma samples were collected from 7 patients every 2 weeks during treatment. Baseline tissue and plasma samples were tested using the 600-genes PredicineATLAS. The study also applied PredicineCNB, a low-pass whole-genome sequencing (LP-WGS) assay, using baseline and longitudinal plasma samples to monitor disease during treatment. Results: The PredicineATLAS assay identified 135 somatic gene mutations and 40 copy number variants among 28 patients. The median tumor mutation burden (TMB) was 4.15 Muts/Mb while the maximum TMB was 14.30 Muts/Mb. The genes with the most common alternations were TP53 (76% in gastric cancer and 64% in colon cancer), APC (24% in gastric cancer and 64% in colon cancer), and MYC (24% in gastric cancer and 64% in colon cancer). Meanwhile, the prevalence of PIK3CA and KRAS mutations was significantly higher in colon cancer than in gastric cancer (PIK3CA: colon 7/11 vs. gastric 2/17, p&amp;lt;0.05; KRAS: colon 8/11 vs. gastric 0/17, p&amp;lt;0.001). Among those 7 patients whose diseases were monitored by PredicineCNB during treatment, 5 patients were observed to have significant decrease in blood-based copy number burden (bCNB) score, after two weeks of treatment. Notably, one colon patient, who has been monitored for 5 timepoints by now, showed continually decreasing bCNB score and reached the criteria of healthy donor judging by an in-house database. Conclusions: This study compared the variation landscape between gastric and colon cancer patients, and demonstrated the technical feasibility of genome-wide copy number variations through liquid biopsy, revealing its potential clinical utility of longitudinal disease monitoring. Citation Format: Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia. Comparative genomic profiling and disease monitoring in unresectable gastric and colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2197.